1. Field of the Invention
The invention relates generally to herpes simplex virus (HSV) vaccines, and more specifically to vaccine compositions of single and multi-antigen HSV subunit proteins, with or without an adjuvant, such as a cationic liposome delivery vehicle, and the uses of these compositions to immunize against herpes simplex virus types.
2. Background Information
Herpes simplex viruses (HSVs) cause human diseases, including, for example, cold sores, eye and genital infections, neonatal infections and encephalitis. There are two serotypes of the virus, the oral form, termed HSV-1 and the genital form, termed HSV-2. HSV-2 infections are the leading cause of genital herpes and the incidence of HSV-2 infection has increased substantially during the past 30 years. It is estimated that in the USA, for example, from 40 to 60 million people are HSV-2 infected, with an incidence of 1-2 million infections and 600,000-800,000 clinical cases per year. Prevalence in the 30-40 year old population is about 30%. Overall prevalence is higher in women than men, especially among the younger population. Moreover, there is increasing evidence that HSV-2 infections contribute to the spread of HIV.
Herpes simplex viruses establish lifelong latent infections within sensory ganglia and therefore recurrent infections are common. Reactivation of virus, i.e. release from latency, occurs periodically over the lifetime of the individual and may result in recurrent infection but always involves virus shedding.
The structure of herpes viruses consists of a relatively large double-stranded, linear DNA genome encased within an icoshedral protein cage called the capsid, which is wrapped in a lipid bilayer called the envelope. The HSV envelope harbors 12 surface proteins and glycoproteins. To deliver the capsid containing the double-stranded DNA genome into the host cell, the virus fuses its envelope with the host's cellular membrane, either at the cell surface or within an endocytic vesicle, depending on the cell type. Among the envelope glycoproteins, gC, gB, gD, gH, and gL participate in viral-cell binding and entry.
HSV remains a significant human pathogen in spite of effective anti-viral therapy. Anti-viral drugs, such as acyclovir, used to treat HSV infections and recurrences, target DNA replication. However, these drugs are administered only when clinical signs appear, but virus shedding occurs even in the absence of clinical signs and is a major source of spread in the human population. Thus, there is an urgent need for an effective HSV vaccine both for prophylactic use and therapeutic use.